Cobimetinib plus vemurafenib (C+V) in patients (Pts) with solid tumors with BRAF V600E/d/k/R mutation: Results from the targeted agent and profiling utilization registry (TAPUR) study.
Authors: Funda Meric-Bernstam, Michael Rothe, Elizabeth Garrett-Mayer, Rodolfo Gutierrez, Eugene R Ahn, Timothy Lewis Cannon, Steven Francis Powell, John C. Krauss, Christopher M. Reynolds, Margaret von Mehren, Deepti Behl, Carmen Julia Calfa, Herbert Leon Duvivier, Henry G. Kaplan, Michael B. Livingston, Manish Sharma, Walter John Urba, Raegan O'Lone, Susan Halabi, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2022)

3008 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pts with solid tumors with BRAF V600E/D/K/R mutation (mut) treated with C+V are reported. Methods: Eligible pts had advanced solid tumors, no standard treatment (tx) options, measurable disease, ECOG performance status (PS) 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts matched to C+V had various solid tumors with BRAF V600E/D/K/R mut, or other BRAF mut if approved by the Molecular Tumor Board, and no MAP2K1/2, MEK1/2, NRAS mut. Recommended dosing was C, 60 mg orally daily for 21 days, 7 days off and V, 960 mg orally every 12 hours. Primary endpoint was disease control (DC), defined as complete (CR) or partial (PR) response or stable disease at 16+ wks (SD 16+) (RECIST v1.1). Low accruing histology-specific cohorts with the same genomic target and tx were collapsed into a single histology-pooled cohort for this analysis. For histology-pooled cohorts with sample size of 28, the results are evaluated based on a one-sided exact binomial test with a null DC rate of 15% vs. 35% (power = 0.84; α = 0.10) and one-sided 90% confidence interval (CI). Other efficacy endpoint estimates are presented with two-sided 95% CIs. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: 31 pts with solid tumors (13 histologies; 6/31 ovarian cancer) with BRAF muts were enrolled from Dec 2016 to Jan 2021 and collapsed into one histology pooled cohort for analysis. 3 pts were not evaluable due to lack of post-baseline tumor evaluation and excluded from efficacy analyses. Demographics and outcomes are summarized in the Table. Pts had tumors with BRAF V600E mut (N = 26), G469V mut (N = 1), K601E mut (N = 2), N581I (N = 1) and T599_V600insT (N = 1). 2 CR (breast and ovarian cancer; V600E), 14 PR (13 V600E, 1 N581I), and 3 SD16+ (2 V600E, 1 T599_V600insT) were observed for a DC rate of 68% (90% CI: 54%, 100%) and an objective response (OR) rate of 57% (95% CI: 37%, 76%). CR durations were 5.1 (ovarian cancer) and 108.9 wks (breast cancer) and median duration of PR was 20.5 wks (range: 8.0, 176.0). 19 pts experienced ≥1 Grade 1-5 AE/SAE at least possibly related to tx including 1 death attributed to tx-related kidney injury. Conclusions: C+V demonstrated evidence of anti-tumor activity in pts with advanced solid tumors with BRAF V600E and other muts . Clinical trial information: NCT02693535. [Table: see text]